Changes of major genes related to cellular senescence in glioma

Changes of major genes related to cellular senescence in glioma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Changes of major genes related to cellular senescence in glioma Nives Pećina-Šlaus, Jan Težak, Klaudia Babić, Andrija Štajduhar, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9084247/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Senescent glioma cells shape the clinical profile of gliomas, playing a key role in clinical outcome and response to therapy. The aim of this study was to analyze the frequency and type of alterations in genes characterized as markers of cellular senescence in different types and grades of gliomas. We analyzed 3425 glioma samples using data from the cBioPortal for Cancer Genomics. After querying 88 genes involved in senescence-associated secretory phenotype (SASP), we selected and studied in detail the 10 most frequently altered ones: TP53 , CDKN2A , EGFR , ATM , TNFRSF1A , IGFBP7 , TNFRSF11B , TP53BP1 , HGF and SERPINE1 . Data analyses included determining the frequency of mutations and copy number alteration(CNA). Additionally, transcript levels, methylation patterns, and survivals were queried for each gene through GlioVis and GEPIA portals, while STRING provided protein network. Our results show that the majority of the studied genes were changed in high-grade gliomas. Genes TP53 , CDKN2A , and EGFR were the most frequently altered ones. TP53, TP53BP1, ATM, HGF were mostly hit by mutations, while TNFRSF1A, TNFRSF11B, IGFBP7, SERPINE1, EGFR by amplifications. CDKN2A was predominantly deleted. The alterations of CDKN2A, EGFR, and IGFBP7 were significantly more frequent in the high grade (HGG) group, while TP53 and TNFRSF11B in the low grade (LGG) group. Patients harboring alterations in SASP genes had significantly shorter overall survival. The expression levels of TP53, TNFRSF1A, TNFRSF11B , IGFBP7, HGF, SERPINE1 and EGFR were significantly higher in HGG, while ATM and TP53BP1 transcript was falling in higher grades. All genes showed significant expression differences according to IDH1 status. mRNA expression levels were associated to levels of methylation for genes ATM , TP53 , and TP53BP1 . Our findings highlight the importance of cellular senescence in glioma progression, and may provide insights for the development of future senomorphics therapies. cellular senescence cBioPortal glioma in silico analysis SASP Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 18 May, 2026 Reviews received at journal 18 May, 2026 Reviewers agreed at journal 18 May, 2026 Reviewers agreed at journal 18 May, 2026 Reviewers agreed at journal 18 May, 2026 Reviewers invited by journal 31 Mar, 2026 Editor assigned by journal 16 Mar, 2026 Submission checks completed at journal 16 Mar, 2026 First submitted to journal 15 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9084247","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":617308623,"identity":"2c7e49c8-8cd5-422e-9997-2bdf9070b6dc","order_by":0,"name":"Nives 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The aim of this study was to analyze the frequency and type of alterations in genes characterized as markers of cellular senescence in different types and grades of gliomas.\u003c/p\u003e\n\u003cp\u003eWe analyzed 3425 glioma samples using data from the cBioPortal for Cancer Genomics. After querying 88 genes involved in senescence-associated secretory phenotype (SASP), we selected and studied in detail the 10 most frequently altered ones: \u003cem\u003eTP53\u003c/em\u003e, \u003cem\u003eCDKN2A\u003c/em\u003e, \u003cem\u003eEGFR\u003c/em\u003e, \u003cem\u003eATM\u003c/em\u003e, \u003cem\u003eTNFRSF1A\u003c/em\u003e, \u003cem\u003eIGFBP7\u003c/em\u003e, \u003cem\u003eTNFRSF11B\u003c/em\u003e, \u003cem\u003eTP53BP1\u003c/em\u003e, \u003cem\u003eHGF \u003c/em\u003eand \u003cem\u003eSERPINE1\u003c/em\u003e. Data analyses included determining the frequency of mutations and copy number alteration(CNA). Additionally, transcript levels, methylation patterns, and survivals were queried for each gene through GlioVis and GEPIA portals, while STRING provided protein network.\u003c/p\u003e\n\u003cp\u003eOur results show that the majority of the studied genes were changed in high-grade gliomas. Genes \u003cem\u003eTP53\u003c/em\u003e, \u003cem\u003eCDKN2A\u003c/em\u003e, and \u003cem\u003eEGFR \u003c/em\u003ewere the most frequently altered ones. \u003cem\u003eTP53, TP53BP1, ATM, HGF\u003c/em\u003e were mostly hit by mutations, while \u003cem\u003eTNFRSF1A, TNFRSF11B, IGFBP7, SERPINE1, EGFR\u003c/em\u003e by amplifications. \u003cem\u003eCDKN2A\u003c/em\u003e was predominantly deleted. The alterations of \u003cem\u003eCDKN2A, EGFR,\u003c/em\u003e and\u003cem\u003e IGFBP7\u003c/em\u003e were significantly more frequent in the high grade (HGG) group, while \u003cem\u003eTP53 \u003c/em\u003eand\u003cem\u003e TNFRSF11B \u003c/em\u003ein the low grade (LGG) group. Patients harboring alterations in SASP genes had significantly shorter overall survival. The expression levels of \u003cem\u003eTP53,\u003c/em\u003e \u003cem\u003eTNFRSF1A,\u003c/em\u003e \u003cem\u003eTNFRSF11B\u003c/em\u003e, \u003cem\u003eIGFBP7, HGF, SERPINE1 \u003c/em\u003eand\u003cem\u003e EGFR\u003c/em\u003e were significantly higher in HGG, while \u003cem\u003eATM\u003c/em\u003e and \u003cem\u003eTP53BP1 \u003c/em\u003etranscript was falling in higher grades. All genes showed significant expression differences according to \u003cem\u003eIDH1\u003c/em\u003estatus. mRNA expression levels were associated to levels of methylation for genes \u003cem\u003eATM\u003c/em\u003e, \u003cem\u003eTP53\u003c/em\u003e, and \u003cem\u003eTP53BP1\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eOur findings highlight the importance of cellular senescence in glioma progression, and may provide insights for the development of future senomorphics therapies.\u003c/p\u003e","manuscriptTitle":"Changes of major genes related to cellular senescence in glioma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-06 14:06:53","doi":"10.21203/rs.3.rs-9084247/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"116478383869161444575881178819825963493","date":"2026-05-19T03:36:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-18T18:00:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"239315823196046093772155711449410182796","date":"2026-05-18T15:09:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"183943744640030484245423882948391149538","date":"2026-05-18T13:21:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319543898743753304560960705034530679320","date":"2026-05-18T12:47:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-31T23:40:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-16T09:49:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-16T06:17:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"Human Genomics","date":"2026-03-15T12:10:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"human-genomics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"hugm","sideBox":"Learn more about [Human Genomics](http://humgenomics.biomedcentral.com/)","snPcode":"40246","submissionUrl":"https://submission.nature.com/new-submission/40246/3","title":"Human Genomics","twitterHandle":"@OAgenetics","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"79e97373-2134-4e33-9a73-974aea1b5240","owner":[],"postedDate":"April 6th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"116478383869161444575881178819825963493","date":"2026-05-19T03:36:16+00:00","index":87,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-18T18:00:26+00:00","index":86,"fulltext":""},{"type":"reviewerAgreed","content":"239315823196046093772155711449410182796","date":"2026-05-18T15:09:44+00:00","index":83,"fulltext":""},{"type":"reviewerAgreed","content":"183943744640030484245423882948391149538","date":"2026-05-18T13:21:54+00:00","index":82,"fulltext":""},{"type":"reviewerAgreed","content":"319543898743753304560960705034530679320","date":"2026-05-18T12:47:30+00:00","index":78,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-06T14:06:53+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-06 14:06:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9084247","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9084247","identity":"rs-9084247","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}